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Vitamin D supplementation at low (600 IU/day) or higher dose (3,750 IU/day) does not improve insulin resistance markers at one year: A randomized controlled trial

Year: 2025
Type: article
Abstract: To compare the performance of newer insulin resistance (IR) indices, triglyceride glucose index (TyG) and metabolic score for IR (METS-IR), with previous markers HOMA-IR and McAuley-IR, and assess the impact of one-year of vitamin D supplementation, at two doses, on these indices in overweight, elderly individuals. Exploratory analyses from a double-blind, multicenter randomized controlled trial involved overweight elderly participants with baseline serum 25-hydroxyvitamin D [25(OH)D] levels of 10-30 ng/ml (clinicaltrial.gov: NCT01315366). Participants received 1000 mg calcium citrate/day and vitamin D supplementation at a low-dose of 600 IU/day, or high-dose of 3750 IU/day. 221 participants received low or high-dose vitamin D supplementation. Mean age was 71 ± 5 years, BMI 30 ± 4 kg/m 2 , 25(OH)D 20 ± 7 ng/ml, with 55% female and 69% with prediabetes. There were no significant baseline differences except for HDL levels (p=0.04). TyG was notably increased in the high-dose group (p=0.02). Mixed linear model analysis showed a greater increase in serum 25(OH)D in the high-dose group compared to the low-dose, with decreases in PTH, cholesterol, and LDL independent of dose. TyG and METS-IR did not differ by dose, time, or dose*time interaction. Subgroup analyses by sex, baseline 25(OH)D cut-off, and glucose tolerance status were null. FokI polymorphism showed a significantly greater METS-IR in the high-dose arm, disappeared after adjusting for fat mass. McAuley-IR was the best IR index compared to TyG and METS-IR, both at baseline and 12 months. Vitamin D supplementation at 3,750 IU/d over one-year did not improve IR markers, including TyG and METS-IR.
DOI: 10.1016/j.metop.2025.100357
Authors: Nancy Safwan, Christos S. Mantzoros, Maya Rahme, Rafic Baddoura, Georges Halaby, Ghada El-Hajj Fuleihan
Institutions: American University of Beirut, Beth Israel Deaconess Medical Center, Harvard University, VA Boston Healthcare System, American University of Beirut Medical Center, Hôtel-Dieu de France
Language: English
Field: Medicine
Open Access status: gold
Estimated APC paid: $2,120
Funders: Foundation for the National Institutes of Health, Office of Dietary Supplements, Mayo Clinic, American University of Beirut, Saint Joseph University, Conseil National de la Recherche Scientifique, Faculty of Medicine, American University of Beirut, Fogarty International Center
OpenAlex ID: W4408326740
FWCI: 0.598
Cites: 38
Cited by: 1
Related to: 10